FDA Approves ADC Therapeutics’ Zynlonta to Treat Rare Cancer

Rare Daily Staff

The U.S. Food and Drug Administration approved ADC Therapeutics’ Zynlonta for the treatment of adult patients with relapsed or refractory large B-cell lymphoma, a rare cancer.

The approval of Zynlonta is for use after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma and high-grade B-cell lymphoma.

Zynlonta, a CD19-targeted antibody drug conjugate, was granted accelerated approval by the FDA based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“There is a significant unmet need for treatment options for patients with relapsed or refractory DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” said Paolo Caimi, a physician at University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University. “Single-agent Zynlonta demonstrated clinically important outcomes in the pivotal LOTIS-2 study across several disease subtypes. Notably, this included transplant eligible and ineligible patients and patients who previously received stem cell transplant or CAR-T cell therapy.”

The FDA approval was based on data from LOTIS-2, a large (n=145) phase 2 multinational, single-arm clinical trial of Zynlonta for the treatment of adult patients with relapsed or refractory DLBCL following two or more prior lines of systemic therapy. Results from the trial demonstrated an overall response rate of 48.3 percent (70/145 patients), which included a complete response rate of 24.1 percent (35/145 patients) and a partial response rate of 24.1 percent (35/145 patients). Patients had a median time to response of 1.3 months and the median duration of response for the 70 responders was 10.3 months (inclusive of patients who were censored). In a pooled safety population, the most common adverse reactions (≥20 percent) were thrombocytopenia, increase in gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain.

ADC Therapeutics said Zynlonta is the first and only CD19-targeted antibody drug conjugate approved as a single-agent treatment for adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL)

DLBCL, the most common type of non-Hodgkin lymphoma in the United States, is a rapidly progressing, aggressive disease that is heterogeneous with multiple subtypes. More than 40 percent of first line DLBCL treatments fail. For patients who fail first-line therapy, prognoses are poor, worsening with each line of therapy as the chance for cure or long-term disease-free survival diminishes.